Our present concept of the mechanism of action of progesterone (in the uterus) is that the hormone is initially bound by some component of the 7S uterine cytoplasmic receptor and that this is one of several biologically important forms of the receptor. Our data, and that of others indicate that under in vitro conditions the receptor may exist in several configurations. The observations may be described by the following equilibria: 4.5S yields (reversibly) 5.5S yields (reversibily) 7S yields reversibly) High Molecular Weight Form (approximately 10S?) Our sedimentation data indicate that one function of progestin (in addition to stabilizing the 7S form) is to drive the equilibria to the right and that biologically potent progestins are preferentially bound by the larger forms. Our researches are designed to substantiate this universal model by determining the effect of various progestins on these equilibria. After determining the association and dissociation rate constants for each conversion, we shall be able to prove or disprove the idea that the biological potency of a ligand resides in its ability to increase the state of aggregation of the receptor, and that larger forms (greater than 7S) are biologically important. Taking advantage of the stabilizing properties of the progestin we shall also isolate and characterize each of the forms of the receptor. This will be accomplished by hydroxylapatite chromatography, G-100 chromatography, preparative sucrose gradient centrifugation and two dimensional electrophoresis.